TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7569	22930;22931;22932	chr2:178721958;178721957;178721956	chr2:179586685;179586684;179586683
N2AB	7252	21979;21980;21981	chr2:178721958;178721957;178721956	chr2:179586685;179586684;179586683
N2A	6325	19198;19199;19200	chr2:178721958;178721957;178721956	chr2:179586685;179586684;179586683
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-60
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.1676
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/I	rs1198203479	0.674	0.044	N	0.347	0.276	0.438170831126	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.17924E-03	None	0	0	None	0	None	0	0	0
T/I	rs1198203479	0.674	0.044	N	0.347	0.276	0.438170831126	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
T/I	rs1198203479	0.674	0.044	N	0.347	0.276	0.438170831126	gnomAD-4.0.0	6.57237E-06	None	None	None	None	N	None	0	6.5505E-05	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.1275	likely_benign	0.1227	benign	-0.411	Destabilizing	0.083	N	0.512	neutral	N	0.506064944	None	None	N
T/C	0.6608	likely_pathogenic	0.6088	pathogenic	-0.211	Destabilizing	0.998	D	0.699	prob.neutral	None	None	None	None	N
T/D	0.5263	ambiguous	0.5089	ambiguous	-1.421	Destabilizing	0.862	D	0.664	neutral	None	None	None	None	N
T/E	0.3598	ambiguous	0.361	ambiguous	-1.376	Destabilizing	0.954	D	0.673	neutral	None	None	None	None	N
T/F	0.2595	likely_benign	0.2421	benign	-0.371	Destabilizing	0.987	D	0.727	prob.delet.	None	None	None	None	N
T/G	0.5128	ambiguous	0.4863	ambiguous	-0.716	Destabilizing	0.882	D	0.65	neutral	None	None	None	None	N
T/H	0.2811	likely_benign	0.2801	benign	-1.251	Destabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
T/I	0.0937	likely_benign	0.0906	benign	0.327	Stabilizing	0.044	N	0.347	neutral	N	0.471066936	None	None	N
T/K	0.1772	likely_benign	0.1744	benign	-0.836	Destabilizing	0.936	D	0.668	neutral	None	None	None	None	N
T/L	0.0991	likely_benign	0.0969	benign	0.327	Stabilizing	0.807	D	0.561	neutral	None	None	None	None	N
T/M	0.0894	likely_benign	0.0872	benign	0.692	Stabilizing	0.991	D	0.704	prob.neutral	None	None	None	None	N
T/N	0.1735	likely_benign	0.1636	benign	-1.067	Destabilizing	0.703	D	0.596	neutral	N	0.466295834	None	None	N
T/P	0.502	ambiguous	0.4622	ambiguous	0.113	Stabilizing	0.906	D	0.72	prob.delet.	N	0.514916501	None	None	N
T/Q	0.2298	likely_benign	0.2378	benign	-1.127	Destabilizing	0.932	D	0.734	prob.delet.	None	None	None	None	N
T/R	0.1529	likely_benign	0.1532	benign	-0.748	Destabilizing	0.987	D	0.721	prob.delet.	None	None	None	None	N
T/S	0.158	likely_benign	0.1564	benign	-1.032	Destabilizing	0.006	N	0.256	neutral	N	0.42806552	None	None	N
T/V	0.108	likely_benign	0.1083	benign	0.113	Stabilizing	0.749	D	0.522	neutral	None	None	None	None	N
T/W	0.668	likely_pathogenic	0.6429	pathogenic	-0.568	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.3107	likely_benign	0.28	benign	-0.246	Destabilizing	0.998	D	0.738	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.